Lymphoid Malignancies

Transcript

• 00:00So today's will be the second part
• 00:03of our series about updates from
• 00:06the American Society of Hematology,
• 00:09with the highlights today focusing
• 00:12on lymphoid malignancy's.
• 00:15As you probably know,
• 00:17we have six sessions within this series.
• 00:19We had the myeloma session last
• 00:21week and this is actually has been
• 00:23recorded and available on the website.
• 00:26For those who could not attend last week,
• 00:29so feel free to check their website and
• 00:31we will also be including the slides
• 00:34for your own reference next week on
• 00:36January 29th will be the update on my
• 00:39load malignancy's February 5th will
• 00:41be pediatric leukemia and acute for
• 00:43plastic leukemia and pediatric oncology.
• 00:45February 12 will be the classical or
• 00:48benign hematology and February 19 will
• 00:50be cell therapy and transplantation.
• 00:52All of those are on Fridays and
• 00:55at 12:00 PM noon.
• 00:59All of those sessions will be recorded
• 01:01and the slides will be available along
• 01:04with the recordings after the sessions.
• 01:07There will be CME credit for those who submit
• 01:10for it at the end of the entire series,
• 01:13and they'll be a form for feedback
• 01:15where we would love to get your
• 01:17input about what you like and what
• 01:20you don't like about the series and
• 01:22how we can improve it going forward.
• 01:24This is the first time we're doing
• 01:27the hematology post ash highlights,
• 01:28and I hope to keep this going for
• 01:31the next few years with a combination
• 01:33of virtual and in person.
• 01:35Components, so for today's session
• 01:38it's a pleasure to have three of
• 01:41our faculty presenting and we will
• 01:44be starting with Doctor Schelling,
• 01:46Kothari or Assistant Professor of
• 01:49Medicine who will go over aggressive
• 01:52lymphoid malignancy's B cell type.
• 01:55Doctor Francis Commentary will
• 01:57cover for us the indolent B cell
• 02:00malignancies and Doctor Turchin City.
• 02:03Also Assistant Professor of
• 02:05Medicine will be covering.
• 02:08The T cell malignancies,
• 02:10both indolent and aggressive.
• 02:13At the end we will have a Q&A.
• 02:16The talks will be around 40 to 45
• 02:18minutes in total and the last 15
• 02:20minutes will have a question and
• 02:22answer session and this will be
• 02:23moderated by our Assistant Professor
• 02:24of Medicine Doctor Scott Huntington,
• 02:26who will be joining at the panel
• 02:28at the panel at the end.
• 02:30So without further ado,
• 02:32I'd like to introduce Doctor Schelling
• 02:33Kothari, who will start us off.
• 02:35Thank you.
• 02:38Thank you Amar.
• 02:44So today I'm going to talk about
• 02:47updates from Astronium 20 focusing
• 02:50on aggressive B cell informers.
• 02:52I'll cover for studies.
• 02:54One very heavily participated and we
• 02:57were one of the top accruing sites of
• 02:59oral triple combination of BTK number M,
• 03:02Tor inhibitor animite,
• 03:04and relapse refractory Richter's
• 03:06transformation and Dean over DL BCL and then
• 03:09I'll talk about more sooner to Zoom app,
• 03:12which is a T cell engaging bispecific
• 03:14antibody in aggressive lymphomas.
• 03:16I will not cover the other 3T cell
• 03:19engaging bispecific antibodies,
• 03:21but they were also presented at.
• 03:23Ash.
• 03:253rd would be the Lima MRD project
• 03:27in mantle cell lymphoma.
• 03:29An Lastly roll off CNS prophylaxis
• 03:31in high risk DLP CL.
• 03:35So this is the first study is the once
• 03:38daily ordered triple combination of
• 03:40the three agents that I talked about in
• 03:43Richter's transformation and in over
• 03:45diffuse large B cell lymphoma. This was
• 03:48presented at ASH 2020 by Doctor Mato.
• 03:53Other preclinical studies.
• 03:56This was a national combination based
• 03:59on synthetic synthetic lethality.
• 04:01As you can see on the left,
• 04:04the tumor volume of in mice drastic
• 04:07drastically reduced in the triple
• 04:10combination arm in comparison to
• 04:12the vehicle or a single agent.
• 04:15On the right you just see the B
• 04:18cell receptor pathway and other
• 04:21pathways that further help.
• 04:23In Onco Genesis an how the triple
• 04:26combination therapy could help prevent
• 04:28tumor resistance by targetting
• 04:30different pathways together,
• 04:31namely employment pathway AKT,
• 04:33mtor pathway, BTK pathway,
• 04:35and I have four inhibition.
• 04:41The key eligibility criteria for this
• 04:443 + 3 design is age more than 18.
• 04:48Life expectancy more than 12 weeks,
• 04:51with other standard inclusion criteria.
• 04:53The stage one, which is what we are
• 04:56presenting today is the BTK monotherapy,
• 04:59like not in combination in one
• 05:02pill but three separate pills of
• 05:05DRM 12 which is the BTK inhibitor.
• 05:08Novel became a bitter in combination with.
• 05:12Letter from Little Mind and
• 05:15everolimus and then eventually.
• 05:18We are will start accruing
• 05:20the Stage 2 instead of three,
• 05:22which is a single pill with
• 05:25three two different drugs,
• 05:26and then eventually all three
• 05:28drugs in one pill for patient
• 05:30convenience and ease of use.
• 05:35This is these other patient characteristics.
• 05:37Here you can see that in
• 05:40Richter's transformation panel,
• 05:41most patients had gotten our chop while in
• 05:44DLB seal all patients had gotten our job.
• 05:48So these patients were heavily treated.
• 05:50Median prior therapies were three in
• 05:52Victor's transformation into Indy.
• 05:54LBC, Elko hurt, so these were in general.
• 05:57The point is that they were
• 06:01heavily pretreated patients.
• 06:03At this is the data,
• 06:05so overall response rate in
• 06:07Richter's transformation is 46%,
• 06:09which is quite phenomenal in
• 06:11in such an aggressive disease,
• 06:13Indian over DLB sell, it was 45%.
• 06:18These are the CRN PR's.
• 06:23This is the waterfall plot,
• 06:25essentially looking at the
• 06:28percentage of tumor reduction.
• 06:31Yellow being the LBC, Ellen blue
• 06:33being Richter's transformation.
• 06:34You see that there is a significant
• 06:37tumor reduction in both the cohorts.
• 06:42Cytopenias were present for sure.
• 06:46Given the triple combination neutropenia,
• 06:4933% grade, 321% grade,
• 06:52429% Grade 3 thrombocytopenia,
• 06:54and 8% Grade 4 thrombocytopenia.
• 06:59The non heme toxicities were low.
• 07:02You know 4% odds are only in one patient
• 07:05and there were no grade for side effects.
• 07:11So the conclusion of this study was
• 07:14that the primary endpoint was met,
• 07:16that the triple combination therapy
• 07:18has an acceptable study safety profile.
• 07:20The main safety findings were expected
• 07:22and manageable, and currently we are
• 07:25accruing for the phase two study.
• 07:28It is underway targeting patients
• 07:30with novel agents exposed to relapse,
• 07:32refractory CLL and other non
• 07:35Hodgkin lymphoma's. Um?
• 07:38The next study I will talk about is
• 07:40the single agent motion resume AB,
• 07:43which is a T cell engaging bispecific
• 07:46antibody and this was presented by Doctor
• 07:49Adam Orlowski from Brown University.
• 07:51And this was studied in the
• 07:53frontline setting,
• 07:54so treatment naive elderly unfit patients
• 07:57with diffuse large B cell lymphoma.
• 08:01Up to 30% of patients aged more
• 08:03than 25 years do not receive
• 08:05standard chemo immunotherapy,
• 08:07so there is a lot of unmet need
• 08:09and there is need to develop
• 08:12therapies which are less toxic
• 08:14more sooner to some apples in IgG,
• 08:16one CD20 CD.
• 08:18Three bispecific antibody that
• 08:20redirects T cells to engage and
• 08:23eliminate malignant B cells.
• 08:25So here Doctor ourselves keep presented
• 08:27early clinical data with single agent
• 08:30most Natuzzi my best first line therapy.
• 08:32The key inclusion criterias,
• 08:34treatment, naive,
• 08:35ideal BCL,
• 08:36patients or high grade B cell informers
• 08:39for patients who were 60 to 79 they
• 08:42they would have to have impairment in
• 08:45adls or inability to tolerate full.
• 08:47Those immunotherapy for whatever reason.
• 08:50Just like with all other
• 08:52bispecific antibody trials,
• 08:53typically it's done in a ramp up
• 08:57fashion to decrease the chances and
• 09:00severity of cytokine release syndrome.
• 09:03Study design allowed pre face therapy
• 09:06with Prednisone and vincristine and
• 09:09responses estimates were done at interim
• 09:11cycle four in Cycle 8 and every six months.
• 09:15There are two doors.
• 09:17Levels are studied 13.5
• 09:19and 30 at the at day 15.
• 09:21So you start with one milligram
• 09:23to milligram in 13.5 or 1,
• 09:26two and 30,
• 09:27and then there was continued every 21 weeks.
• 09:32Patient population is shown here.
• 09:34So 29 elderly unfit patients were
• 09:36enrolled in this study of eight
• 09:38patients less than 80 years old.
• 09:40Five patients had impairment in
• 09:42renal function. As you can see here,
• 09:44performance status, you know 022.
• 09:47We do see clinically patients who
• 09:49have worse performance status,
• 09:51but given the clinical trial design,
• 09:53it isn't. It is quite understandable
• 09:55that they were enrolling 022.
• 09:58Quite a few. Almost 50% of Asia.
• 10:00With stage four disease and 50%
• 10:03with elevated elevated LDH,
• 10:05so overall a good real world
• 10:07characterization of patients here.
• 10:12Side effects were present,
• 10:14but relatively easy to manage,
• 10:16so rash, fatigue, abdominal pain,
• 10:19infusion related reaction,
• 10:20decreased appetite and dry mouth.
• 10:22Cytokine release syndrome was also present,
• 10:25but the grade three and four
• 10:28CRS events were very low.
• 10:32The best oral response rate was
• 10:36seen in in 6363.5% of patients
• 10:39and in the highest dose cohort,
• 10:4230 milligrams. 50% of the patients
• 10:46achieved complete response.
• 10:50This is still sure the
• 10:52durability of response.
• 10:53The ones in green are the
• 10:56patients with complete response
• 10:58and most of them continue to
• 11:00enjoy the durable response rate.
• 11:02Immediate duration of response
• 11:04was not reached and this is only
• 11:07a 5.4 months of median follow-up,
• 11:09so clearly very early data an we need
• 11:12to wait for the data too much or.
• 11:18So these are the authors conclusions
• 11:20early clinical data indicates that single
• 11:23agent is manageable and acceptable.
• 11:25Has acceptable safety profile.
• 11:27Encouraging efficacy was seen in this
• 11:29setting, an although they did some
• 11:31correlated studies and they did not find
• 11:34any clear Association with peripheral
• 11:37T cell activation and response.
• 11:39This paves way for either single agent or
• 11:42combination therapies with most senators.
• 11:44Mab in frontline setting,
• 11:46especially in elderly unfit.
• 11:48Patients.
• 11:48The third study I would like to
• 11:51talk about is the predictive power
• 11:53of early sequential MRD monitoring
• 11:55in mental cell lymphoma following
• 11:58autologous stem cell transplantation
• 12:00with or without rituximab maintenance.
• 12:04This was presented by Doctor Callanan
• 12:07on behalf of the Lisa Group.
• 12:09The study was designed as such so the
• 12:12patients with classical mantle cell
• 12:14lymphoma had baseline MRD analysis
• 12:17done followed by 4 cycles of our dehab
• 12:20followed by pre autologous tense,
• 12:22transplant,
• 12:22MRD analysis and then you know high
• 12:25dose chemotherapy and then again post
• 12:28autologous transplant MRD analysis and
• 12:30then patients were either randomized to
• 12:33trucks or maintenance or observation.
• 12:35That type of MRD that was done was.
• 12:39Yeah,
• 12:40so IGHQ PCR.
• 12:42Looking at VDJ recombination region.
• 12:47Am the only talk about the first name
• 12:49given in interest of time is the
• 12:51prognostic impact of MRD status pre
• 12:54and post autologous stem cell transplant.
• 12:59This is the survival curve for pre
• 13:01autologous stem cell transplant,
• 13:03MRD status, so the one in red is MRD,
• 13:06negative green, blue is MRD positive so
• 13:09you can see that there is clear split
• 13:12in PFS and OS with improvement in PFS
• 13:14and OS in patients with MRD negativity.
• 13:20And hence essentially,
• 13:21this figure shows that there is a
• 13:23prognostic value in in doing MRD analysis.
• 13:26The next question that the authors
• 13:28looked at was to look at impact of
• 13:32maintenance therapy and MRD negative
• 13:34patients so the one the curve in
• 13:36red is patients who got Rituxan.
• 13:38Mab were but were not MRD negative
• 13:41and in blue is patients who are an
• 13:44observation and were MRD negative so you
• 13:47can see that even though these patients.
• 13:49MRD negative that is a clear split and
• 13:52that is you know statistically significant
• 13:55difference with PFS OS benefit in
• 13:58patients who got rituximab maintenance.
• 14:01The same thing holds true
• 14:03for post autologous stem,
• 14:04cell transplant, MRD also.
• 14:06Hence, the data is a bit humbling.
• 14:09Where we would you know would love
• 14:12to use MRD for therapeutic decisions,
• 14:15but it is pretty clear that maintenance
• 14:18rituximab still remains gold standard
• 14:20in classical mental cell lymphoma and
• 14:23it's definitely a proof of concept
• 14:25that MRD is a good prognostic tool
• 14:27and should be used in addition to
• 14:30other tools such as pet imaging.
• 14:35Lastly, I will talk about CNS prophylaxis
• 14:37in aggressive non Hodgkin lymphoma's.
• 14:39There were two abstracts presented in the
• 14:43oral session at ASH 2020 and both kind of
• 14:46guide us in different directions in terms
• 14:49of what we do in clinics as of today,
• 14:52but there is a big caveat that both are
• 14:56retrospective studies and I would say
• 14:58that we need more prospective data before
• 15:02we change our or practice patterns.
• 15:05Traditionally, the CNS relapse risk
• 15:07is calculated as CNS IPI scoring,
• 15:10which includes age, ekach status,
• 15:13LDH, stage of the patient.
• 15:17The number of external sites and
• 15:20kidney and adrenal involvement.
• 15:22So patients who have intermediate
• 15:24or high CNS IPI score are thought to
• 15:28benefit from from CNS prophylaxis,
• 15:31mainly high dose Ivy methotrexate.
• 15:35Rather than intrathecal methotrexate.
• 15:39The first study that I'll talk about here.
• 15:43Their objective was to determine if high
• 15:46dose methotrexate reduced CNS relapse rates
• 15:49and this was based in Alberta, Canada.
• 15:51The design was retrospective include
• 15:54patients were 18 to 70 years of age with
• 15:59DL BCL treated between 2012 and 2019.
• 16:02These patients CNS involvement at
• 16:05diagnosis were excluded, as evident here.
• 16:10What is interesting is that at this
• 16:12site where they had identified
• 16:14high risk patients only out of 326
• 16:17identified high risk patients,
• 16:19only 115 had gotten high dose methotrexate
• 16:21for unknown reasons to under 911 patients
• 16:24did not get high dose methotrexate,
• 16:26so right off the bat you know since
• 16:29we are analyzing only 115 patients,
• 16:32it's difficult to make any
• 16:34strong conclusions.
• 16:35But here high dose methotrexate was
• 16:37used was associated with younger age,
• 16:40more the next one external site
• 16:42could bring additional involvement
• 16:44and double hit lymphoma.
• 16:47Multivariate analysis is shown here
• 16:50where you can see that the. There was no.
• 16:55Reflected high dose methotrexate did
• 16:57not show any improvement in CNS relapse
• 17:01and the same holds true for intensive
• 17:04immunochemotherapy such as our dose
• 17:06adjusted epoch or are high perceive.
• 17:08Add in comparison to R.
• 17:10Chop consolidative autologous
• 17:11stem cell transplantation was
• 17:13definitely showed more impact,
• 17:15although it did still cross the.
• 17:19Hazard ratio of 1.
• 17:22Here I'm showing multivariate
• 17:24analysis for PFS and OS.
• 17:27You can see that prophylactic high
• 17:29dose methotrexate and intensive
• 17:30immunochemotherapy did not show any
• 17:33statistically significant difference,
• 17:34although there was difference
• 17:36in PFS and OS in consolidative,
• 17:39autologous stem cell transplanted patients.
• 17:42Authors conclusions were there CNS
• 17:44relapse affect 6% of DCL patients and
• 17:47risk of CNS relapse or similar with
• 17:50or without high dose methotrexate and
• 17:52and as a proof of concept similar to
• 17:56rates reported in prior publications.
• 17:59Consolidative autologous stem
• 18:01cell transplantation or intensive
• 18:03immunochemotherapy trended to reduce CNS
• 18:06relapse of finding that is worthy of
• 18:09further study in a prospective setting.
• 18:12The other study that I will quickly go
• 18:16over before I hand over to Doctor said
• 18:19he is the CNS relapse by prophylaxis route.
• 18:23So the this study was a US multi
• 18:27center retrospective study where they
• 18:29found that from all the centers with
• 18:33patients 100 and 1000 patients total
• 18:365.5% had overall CNS relapse rate of
• 18:39the patients who got into tickle.
• 18:42CNS prophylaxis,
• 18:435.3% had CNS relapse and of the patients
• 18:47who got intravenous prophylaxis.
• 18:49Seven point, 1% had CNS relapse.
• 18:55So there there are many other
• 18:57findings from this study,
• 18:58but in interest of time,
• 19:00I'll briefly discuss their conclusions.
• 19:03What I found interesting from this study was
• 19:06that not only CNS IPI scoring is important,
• 19:09but they also found a significant
• 19:11CNS relapse rate in patients who
• 19:14had involvement of testis or liver.
• 19:16So that's something that we should keep
• 19:19in mind in our clinics, but overall,
• 19:22you know CNS relapse rates were similar,
• 19:25following prophylaxis,
• 19:25either intrathecal or high dose methotrexate.
• 19:28They are going to do comparisons of
• 19:30single versus dual route so intra fickle.
• 19:33In high doses in the future and also
• 19:36compare pro flexes and no pro flexes,
• 19:38which would I think be of interest
• 19:40to all of us?
• 19:41But overall outcomes for following
• 19:44CNS relapse remain poor without clear
• 19:46benefit from existing treatment options.
• 19:51Thank you and please use the chat
• 19:53window for questions while we go
• 19:55along with more presentations.
• 20:43Hi everyone. So I'll be presenting
• 20:47the update on primarily focusing
• 20:50on the Salem farmers. And.
• 20:55So just one at a couple of
• 20:58abstracts for indolent lymphoma.
• 21:00I have no relevant disclosures.
• 21:04So just starting with a brief overview.
• 21:09You know, dealing with the challenging
• 21:11field of T cell informers.
• 21:14You know there were a few studies
• 21:16that were presented that are off.
• 21:19Note that I'd like to highlight it in
• 21:22frontline peripheral T cell lymphoma.
• 21:24A couple of studies including the combination
• 21:27romidepsin job and as I said in chapter.
• 21:30Presented in relapsed refractory
• 21:33PTCL we had an update.
• 21:36On developer and relapsed refractory CDCR.
• 21:39There was a novel interleukin
• 21:41antagonist BNZ one,
• 21:43and then I will shift gears in
• 21:46touch on a couple of CLL studies.
• 21:50At the end.
• 21:52So talking about property selling
• 21:55former really the frontline treatment
• 21:58of this aggressive disease is a
• 22:00major area of clinical need and.
• 22:05You know, we most of us have been using
• 22:08CHOP or chop like regiments as the backbone
• 22:11chemotherapy backbone of frontline therapy.
• 22:14However, unfortunately,
• 22:15unlike diffuse large B cell lymphoma
• 22:18where our job has almost doubles,
• 22:20the CR rates that are seen with PTCL.
• 22:23So with PCL, which job we're looking
• 22:27at CR rates of just 35 to 40% in the
• 22:31setting of an aggressive lymphoma.
• 22:33This is really.
• 22:35A very challenging situation.
• 22:38Chip has been studied and shown to be
• 22:41of some limited success in certain in
• 22:44subtypes of patients in a subset of patients,
• 22:48specially those younger than 60 years of age.
• 22:52Much higher toxicity was seen in.
• 22:56Higher age group and those adjusted are.
• 23:01Suggested the bug is really considered
• 23:04for more aggressive subtypes like ATL and
• 23:08clinically aggressive presentations of PTCL.
• 23:11It's only recently that.
• 23:14No one study has changed the
• 23:16standard of care in CD.
• 23:1830 positive.
• 23:20TCL primarily in LCL Septics,
• 23:22where which where there was the most robust
• 23:25data for the combination of brentuximab,
• 23:28CHP from the Echelon two trial.
• 23:31But outside of this you know other studies
• 23:34that have tried to build on the chop
• 23:37backbone have not been very successful.
• 23:43So with this I'm going to present
• 23:46two frontline trials for PTCL,
• 23:48frontline treatment and
• 23:50so starting with Rd shop.
• 23:52So this was a phase three.
• 23:56A study conducted by the Lisa Group and
• 23:59again a frontline treatment of PTCL.
• 24:03It was presented by Doctor Vashi.
• 24:06So this study was based on the
• 24:09Phase 1B prior Phase 1B data.
• 24:13That showed. Basically a phase two
• 24:18dose of 12 milligram per meter squared
• 24:21was the one that was associated with,
• 24:24you know, but the best safety data
• 24:27given on day one and data for 21 day
• 24:31cycle with CHOP given on day one.
• 24:34This particular this is this
• 24:36prior study did have.
• 24:38Basically they give 8 cycles and a
• 24:41total of about 37 patients were studied.
• 24:45So in this present study presented
• 24:48by Doctor Bashi,
• 24:49this was a randomized controlled
• 24:51trial phase three data where
• 24:54the army was chop alone,
• 24:56and then I'm be had romidepsin,
• 24:58given in addition to chop again
• 25:01days 121 and eight at a dose of
• 25:0412 milligram per meter squared.
• 25:06The recommended phase two dose
• 25:09from the Phase 1B study.
• 25:12So in the study population,
• 25:15I do want to highlight that like
• 25:18many T cell lymphoma trials,
• 25:21it did include a very heterogeneous
• 25:24population of all aggressive
• 25:27histologies and then also looking at.
• 25:30One thing that is relevant really
• 25:33here is that patients undergoing
• 25:35autologous or allogeneic transplant
• 25:37planned as a consolidation
• 25:40were excluded from this study,
• 25:42which is really important to note because.
• 25:47A lot of people,
• 25:49even based on controversial data
• 25:51you consider autologous stem cell
• 25:53transplant for most patients who are
• 25:56eligible in first remission after
• 25:59after frontline treatment of PCL.
• 26:02The primary endpoint of this study
• 26:05was progression free survival and
• 26:07secondary endpoints included safety as
• 26:10well as additional efficacy endpoints.
• 26:13Again,
• 26:13baseline characteristics I want to
• 26:16highlight about half of the patients
• 26:19were of a ITL subtype and then,
• 26:22as expected,
• 26:23PCL and LCL where the other common subtypes.
• 26:28So here, unfortunately,
• 26:30like many other studies.
• 26:32But that have used chopped backbone.
• 26:35This was a this study did not
• 26:37meet its primary endpoint of
• 26:39improved progression free survival.
• 26:42The hazard ratio.
• 26:44For Rd shop versus R Chop Chop was
• 26:49appointed one with a P value of .096.
• 26:54And again,
• 26:55a subgroup analysis based on
• 26:57where this IPI factors.
• 27:00As well as histologies did not
• 27:02really show any significant
• 27:04subsets that were that achieve
• 27:06greater benefit from this regimen.
• 27:08But patients with AI TL did have.
• 27:11There was a trend too.
• 27:15Some benefit in this particular population,
• 27:18again looking at the overall
• 27:20and the complete response rates,
• 27:22the complete response rate was
• 27:2541% compared with 37%,
• 27:27which is consistent with
• 27:29historical data that we have from.
• 27:32Job. Again, without.
• 27:37Fighting any increase, additional efficacy.
• 27:39Rd job was more toxic.
• 27:42A substantial number of patients
• 27:44were not able to receive all
• 27:47doses of romidepsin as well as
• 27:50job and also significant number of
• 27:53patients are received.
• 27:55Had to undergo jobs reduction or
• 27:58interruption because of increased toxicity,
• 28:00which is primarily increased.
• 28:04Haematological toxicity so really,
• 28:07in summary for this study,
• 28:10Roach up increase toxicity without
• 28:13improving efficacy in frontline
• 28:15treatment of PTCL possible future
• 28:17directions really is based on
• 28:19whether CHOP is the right backbone.
• 28:22We do notes there.
• 28:24Drugs like romidepsin are more
• 28:26active in certain subtypes of
• 28:28PTCL like PTCL with T follicular
• 28:31helper, cell subtype and AI TL
• 28:34and so maybe's patient selection.
• 28:37And based on Histology and then there
• 28:41is another trial that is being.
• 28:44And that is yet to start accruing.
• 28:46But it's basically has been proposed
• 28:48by NCI where they're looking at the
• 28:51combination of Doxorubicin 5 as a as
• 28:53a sighted in oral and then romidepsin
• 28:56and develops it in T cell lymphoma.
• 29:00So those would be, you know,
• 29:02interesting things to look forward to.
• 29:04Our next study that was presented
• 29:07in Frontline PTCL was oral,
• 29:10is cited in CC-486 plus job.
• 29:13This was presented by
• 29:16Doctor Rowan from Kernel.
• 29:19So again, this particular study
• 29:21actually highlighted the point that
• 29:23an oral PCL with T follicular helper
• 29:26cell subtype is associated with.
• 29:30My hyperventilating mutations
• 29:32in the Ted in Ted 2D N MT3A and
• 29:36IDH 2 an in addition also roue
• 29:39mutations and this was the rational.
• 29:42These mutations are not only present
• 29:44in the two T follicular helper cell
• 29:48subtype AI TL but also some PTCL,
• 29:51PTCL nosc and so that was the
• 29:55rationale for using is cited in.
• 29:59As an epigenetic.
• 30:01Timer with chop.
• 30:04So this they proceeded straight to
• 30:06a phase two study because there was
• 30:09Phase one data for safety of this
• 30:11combination from B cell lymphoma.
• 30:13Uh, the they do.
• 30:15They do include all PTCL subsets.
• 30:18However they did prioritize enrollment
• 30:21of the T follicular helper cells
• 30:24upset and as you will see of the 20
• 30:28patients 17 where of TFH subset here?
• 30:31The primary endpoint was complete
• 30:34response rate and secondary endpoint
• 30:36was overall response rate and safety.
• 30:39They also looked at some genomic
• 30:42markers so this was an. Interesting.
• 30:47Study design and treatment regimen where
• 30:50initially CC 486 was given as a lead
• 30:54in from day minus 6 two day one for
• 30:57the first cycle and then subsequently
• 31:00from and subsequently four cycles.
• 31:04125 they received CC-486 on.
• 31:09Days 8 to 21 which basically
• 31:12so every so for cycle one.
• 31:15So this present this acted as priming
• 31:17phase for the next cycle of chemotherapy.
• 31:24So. After 21 patients that were enrolled,
• 31:2820 were evaluable for response
• 31:30and of these almost half of them.
• 31:33These patients actually did go on to
• 31:36receive autologous stem cell transplant
• 31:39or or one patient who received Alo.
• 31:42Here we see the overall CR overall
• 31:45response rate in CR rate in these
• 31:48patients in these 20 patients,
• 31:50and of all, all patients considering
• 31:53all patients as well as patients with
• 31:56PTCL default color helper cell subtype.
• 31:58It was seen that.
• 32:0188% CR rate was seen in TFs subtype
• 32:06compared with 75% all comers.
• 32:08Really, majority of the patients
• 32:11were of TFs subtype.
• 32:13Here are the results from the here.
• 32:16The survival curves,
• 32:17so the median follow up of 15 months.
• 32:22One year PFS was 66% for all patients
• 32:26and one year overall survival was 80%
• 32:30and the corresponding numbers for
• 32:32TFs subtype were almost 70% and 94%.
• 32:38This was a relatively well tolerated
• 32:41regimen with expected side effects of.
• 32:45Aside opinion, specially neutropenia,
• 32:47but other than the hematological toxicity,
• 32:51there were no additional
• 32:54significant unexpected side effects.
• 32:56This study also looked
• 32:58at mutational analysis,
• 32:59and it's worth mentioning that they
• 33:01found that tattoo was associated
• 33:03with a favorable prognosis in this
• 33:06cohort of patients and DMD MT3.
• 33:08Oh was associated with
• 33:09worse overall survival.
• 33:13So this was a surprisingly promising
• 33:15study and of this combination.
• 33:17Again, this is very early
• 33:20data of only 20 patients.
• 33:22So this is a, you know,
• 33:25a combination that is being tested further.
• 33:28One particular study that is worth
• 33:31highlighting is this alliance study,
• 33:33which is actually going to be rich is going
• 33:37to include patients with a C30 negative.
• 33:41PTCL non alc else Histology and it
• 33:44has it had three comparator arms one
• 33:48including CC 4861 including development
• 33:51and the third one is Chopper show up here
• 33:54with these combination they are using
• 33:57the backbone of Cho Absolute as well.
• 34:00It'll be worth looking at the.
• 34:05We can see. Of this these combinations.
• 34:11Next, I'd like to go onto a
• 34:14study with Dibella sub again,
• 34:16another promising new agent
• 34:17and T cell lymphoma.
• 34:19This was in relapsed refractory
• 34:21peripheral T cell lymphoma and
• 34:23this was updated data from the
• 34:26phase two Premier trial where they
• 34:28looking at those optimization and
• 34:30I'll go over that a little bit.
• 34:33This was presented by Doctor
• 34:35Pro from Northwest.
• 34:39So dualism is a dual appear
• 34:41three kindness Delta inhibitor.
• 34:42We know that is FDA approved
• 34:45in relapsed refractory,
• 34:46follicular lymphoma and CLL and
• 34:48the doors in these patients in
• 34:50these two diseases they approved
• 34:52doses 25 milligram vid when they
• 34:54tested this dosin T cell lymphoma.
• 34:56the Mac the MTD was 75 milligram
• 34:59PID vid and that was the dose
• 35:01tested in T cell lymphoma which
• 35:04showed an overall response rate
• 35:06of 50% in relapsed refractory,
• 35:08PTCL and 33% in cutaneous T cell.
• 35:11Former.
• 35:12So the reason that was the reason for
• 35:14designing this dose optimization study
• 35:16was to see whether these patients
• 35:19truly need 75 milligrams pob ID.
• 35:21Or are we overtreating them?
• 35:24So the study design.
• 35:26Again, there was a dose optimization
• 35:28phase followed by those expansion phase.
• 35:30It did include.
• 35:33The various,
• 35:35not subtypes that we discussed and.
• 35:40So develop the cohort one included patient
• 35:42develops if patients received develops.
• 35:45If 25 milligram B ID and cohort two.
• 35:48They received 75 milligram
• 35:50vid as the starting dose.
• 35:52The primary endpoint was overall
• 35:55response rate with these two doses
• 35:57and then the secondary endpoints
• 36:00again looked at additional
• 36:02safety and efficacy endpoints.
• 36:04So here we are looking at cohort one and
• 36:07go to each had 13 evaluable patients.
• 36:11So the overall response rates.
• 36:14Sorry so the overall response rates.
• 36:16Seen here with the 25 milligram.
• 36:20I was basically 35 to 40% by the
• 36:24investigator and the committee
• 36:26and compared with 75 it was
• 36:28a higher response rate.
• 36:30Overall response rate of 54 to 62% and
• 36:34then similar trends being seen in CR rates.
• 36:39When they looked at looking
• 36:41here at the waterfall plot,
• 36:43it was seen that all the early
• 36:45dropouts based of you to progression
• 36:47were in the 25 milligram dose cohort,
• 36:50and therefore they did in those expansion
• 36:54phase they decided to go on with.
• 36:57Using a adoes starting with a dose
• 37:00of 75 milligrams vid for two cycles.
• 37:03In those patients who had Disease Control,
• 37:06they would go on to receive
• 37:0925 milligrams pob ID.
• 37:12And now with this combination of doses,
• 37:16an overall response rate of.
• 37:2250% was seen with the CR rate of
• 37:2536% and so there there for this was
• 37:28the overall those expansion phase,
• 37:31including included 25 patients and
• 37:33this is a swimmer plot showing the
• 37:36duration of response for these patients.
• 37:42Again, in terms of side effects,
• 37:45there were no unexpected side effects,
• 37:48and the combination of those
• 37:50where you know those reduction
• 37:5225 milligram was associated with
• 37:55better tolerability overall.
• 37:59So again, this study highlights
• 38:01that develop is definitely an active
• 38:03agent in T cell lymphoma specific,
• 38:06especially in relapsed refractory PTCL.
• 38:08And that this going forward.
• 38:11This study provides data.
• 38:15For using this dual dose of 75 milligram,
• 38:19starting those with 25 milligram.
• 38:22Having a. Efficacy while balancing
• 38:26the toxicity of this single agent.
• 38:31So the last. See the last
• 38:36study in T cell lymphoma.
• 38:38Later, like to highlight is that and this
• 38:42is I'm going to go over this very briefly,
• 38:46but this looked at knew novel
• 38:49Interleukin antagonist.
• 38:50Starting the call going ambition of
• 38:53aisle to aisle 9 and I'll 15 by BNZ 1.
• 38:57And this was studied in a Phase 1
• 38:59two study and it was presented by
• 39:02Doctor Klarfeld from City of Hope.
• 39:05Today study different dose levels
• 39:08and it was those level two of two
• 39:12milligram per kilogram was decided as the.
• 39:16Phase two day for phase two dose based
• 39:19on the PK PD data there there was
• 39:22this drug was not associated with any
• 39:25major side effects and so therefore
• 39:28there was no MTD and based on the.
• 39:32So considering everything,
• 39:33including the efficacy data
• 39:34they discarded around to,
• 39:35go ahead with the dose of
• 39:382 milligram per kilogram.
• 39:40So this I want to highlight the fact
• 39:43this is was a really highly refractory
• 39:46population of CCL patients with medium
• 39:49file median 5 prior lines of therapy
• 39:53and without any major side effects of
• 39:56an overall response rate of 52% was seen.
• 40:00A subset of patients which is
• 40:03definitely makes this a very promising
• 40:05agent to go further in studies.
• 40:08They do did highlight that you know
• 40:12being targeted blocker of aisle
• 40:14to aisle 15 an aisle 9.
• 40:16It has a 3 prong.
• 40:19I can see where.
• 40:22Including direct anti tumor effect.
• 40:25Reduction of T regs and basically
• 40:28activation of anti tumor immune
• 40:30response and then also an anti
• 40:33inflammatory effect seen through
• 40:35I'll 15 blockade which is relevant
• 40:37for patients with PTCL who have a
• 40:40robust inflammatory reaction that
• 40:42leads to mobility in this disease.
• 40:47So with that,
• 40:48I'd like to quickly shipgirls too,
• 40:51and I will go through this very briefly.
• 40:54A couple of CLL abstracts,
• 40:56so the first one is locked, so 305.
• 40:59This is the next generation,
• 41:01highly selective non covalent BTK inhibitor
• 41:04in previous previously treated CLL SLL.
• 41:07And this was a Phase 1 two
• 41:10study presented by Doctor Matot.
• 41:12So lock the three or five.
• 41:15It's as previously mentioned,
• 41:17the highly selective non covalent BTK
• 41:20inhibitor in it inhibits both wild
• 41:22type as well as C481 mutated BTK.
• 41:25So when we see look at patients
• 41:27who have a BTK resistance,
• 41:29the most common cause of that is
• 41:32because of the mutations in BTK.
• 41:34And this drug does target
• 41:37that population of patients.
• 41:40But this was a these patients
• 41:43were heavily pretreated,
• 41:44including patients who had
• 41:46failed or discontinued,
• 41:48became a better for due to toxicity
• 41:51and also had this is a high risk
• 41:55population of patients with 17 P
• 41:58deletion and TP 53 mutation present
• 42:01present in a total of over 50% of patients.
• 42:07So the Phase one study,
• 42:09so the date data presented is
• 42:12from the Phase one study which
• 42:14included patients with CLL and SLL.
• 42:17And.
• 42:19Uh.
• 42:23This loss of three or five
• 42:26safety profile was unique,
• 42:27as in the the most common grade three side
• 42:32effect was actually fatigue and the typical.
• 42:36Side effects associated with other BTK
• 42:40innovators like atrial fibrillation.
• 42:42The side effects were not very
• 42:45prominent with locks or two or five.
• 42:48Since there was no DLT's,
• 42:49the maximum tolerated dose was not reached,
• 42:52and. Based on the PK data and the efficacy
• 42:57data dose of 200 milligrams was decided
• 43:00as the recommended phase two dose.
• 43:03Again, here it was in a heavily
• 43:05pretreated well population.
• 43:07Locks or three or five was found to be.
• 43:11Continue to have.
• 43:13Made up a very good efficacy in this.
• 43:17Beta in this patient population and looking
• 43:22at the overall response rate of 63%.
• 43:26So it was.
• 43:28It was a very.
• 43:30Good basically good response in
• 43:31this without a lot of toxicity
• 43:34in this patient population.
• 43:38So lots of three or five was
• 43:40active at all those levels,
• 43:42and typical became a bitter or
• 43:44related toxicities were not seen.
• 43:46These responses were independent,
• 43:48BTK mutation and even patients who
• 43:50had received BCL two inhibitor.
• 43:52When I took LAX as well as
• 43:54three kinase inhibitors,
• 43:55did respond to this drug.
• 43:57So there's a safety and
• 43:59efficacy signal in CLL.
• 44:01Yeliz will be passed participating in
• 44:03the phase two portion of this data.
• 44:06Of this study.
• 44:09Um? And then finally I just want to
• 44:12mention this particular study that
• 44:14was open at Yale in the past and
• 44:18that is umbrella civs and you've
• 44:20lytic seemab you two study which
• 44:23used a novel dual inhibitor π,
• 44:25three kinase and casein kind
• 44:27is money in a better and.
• 44:32The only issues with this study was
• 44:34that you know the comparator arm
• 44:37was a bit as a map chlorambucil,
• 44:39which is not really a very
• 44:41relevant in this day and age,
• 44:44at least for treatment naive patients.
• 44:46But this is being studied further
• 44:48in combination both in frontline
• 44:49and relapsed refractory setting.
• 44:54That's all I have.
• 45:16Tell everybody.
• 45:28Hello everybody, I'm going to go over the.
• 45:32Abstract relevant to heart killing
• 45:35form for the sake of time I'll
• 45:38try to be brief and uncover only
• 45:41heart killing form at this time.
• 45:44So since the introduction of Brentuximab and
• 45:47Odin and checkpoint inhibitors in general,
• 45:49the paradigm of treatment for this
• 45:52disease is changed substantially, and.
• 45:57And this agent,
• 45:58that now you been used earlier and
• 46:01earlier in the course of the disease.
• 46:03So I will review the knew,
• 46:05the updates and the new data relevant
• 46:08of the uses regarding the using of
• 46:10these agents in first line in the
• 46:12relapsed refractory setting and maintenance.
• 46:15Adding after transplant and
• 46:17in the elderly population.
• 46:19So let's start with that.
• 46:20The five year update of action on one,
• 46:23as we all know, this is a.
• 46:26A very large open label,
• 46:28multicenter randomized phase.
• 46:30Three study that was initially presented
• 46:33at three years ago at the Ash meeting
• 46:35with a 2 year follow up over 1300
• 46:39patients were randomized either to get
• 46:41brentuximab avd for six cycles or abvd,
• 46:44which is the standard treatment at
• 46:47city was performed after two cycles,
• 46:49but this was not a pet adapted approach.
• 46:52The primary endpoint of the
• 46:55study was a modified PFS.
• 46:58Which is which included time to progression
• 47:00that and not completely response
• 47:02and use of subsequent chemotherapy.
• 47:05This modified PFS was meant to capture
• 47:07all the events that reflected the failure
• 47:10of frontline treatment and patient
• 47:12and were followed up with the serial imaging.
• 47:15The first data set that was presented
• 47:19from this dialogue after a follow up
• 47:22Papa to essentially two years showed
• 47:24a benefit in using a plus abvd A plus.
• 47:27Abd compared to a DVD with an
• 47:31absolute in benefit of 5%,
• 47:33this modified progression free
• 47:35survival was 82 versus 77.
• 47:37This came at the cost of significant
• 47:41increase in side effects.
• 47:43Neutropenia 58% versus 45 from Europe.
• 47:46But there was a big big one
• 47:49with a 67% incidents.
• 47:51An informercial city was the one that
• 47:55was reduced due to the omission of the.
• 47:58Bleomycin.
• 47:59So why this is the five year
• 48:02five year update is important.
• 48:05We nearly all recurrences of Hodgkin
• 48:08lymphoma happen usually within five years,
• 48:10so we think that PFS of five year
• 48:13is a good surrogate for for cure
• 48:16an here the five year data we
• 48:19do see the PFS for the A plus.
• 48:22Avd is the red curve 82% of five
• 48:26years compared to 75% in the
• 48:28ABVD Ann and these disadvantage.
• 48:30And that was observed initially
• 48:32persisted overtime maybe depend.
• 48:34And this was how they threw in
• 48:37in patients achieving the path
• 48:39to negativity after two cycles.
• 48:41This hopper curb is 2 cars here compared
• 48:44to those that were at negative.
• 48:47So this was not a fat adapted approach.
• 48:50Again,
• 48:50the rates of if you remember the
• 48:53data from this work started.
• 48:55Yes,
• 48:55816 trial where patients had positive
• 48:57after two cycles received ended up
• 49:00receiving escalated Beacopp for six cycles.
• 49:02This PFS compared favorably to
• 49:04patients that received and much more
• 49:06aggressive course of treatment with a
• 49:08very high rate of secondary malignancies,
• 49:11and based on the profile and
• 49:13different risk characteristics.
• 49:14Applications are in the trial.
• 49:17Or the essentially all the group favored
• 49:20the use of brentuximab plus avd.
• 49:23So I think that was a highlighted
• 49:25and I think
• 49:26it's very important to note is
• 49:29that the peripheral neuropathy,
• 49:31which was one of the concern major concern
• 49:33when the initial results were released,
• 49:36has really improved or complete.
• 49:38Completely resolved in the vast majority of
• 49:42the patient and with an improvement that.
• 49:45Happened progressively over the
• 49:47course of the years and currently
• 49:49patients will receive one.
• 49:50Prefer neuropathy, have a really low
• 49:52grade of peripheral neuropathy, if any.
• 49:54Another thing that was noted in
• 49:56this five year update is that
• 49:58the rate of secondary malignancy.
• 50:00And the rate of successful
• 50:03pregnancies compared well to the ABVD.
• 50:05Um, so I think that with this five
• 50:08year update of the action and one,
• 50:10we have more compelling.
• 50:13Data now to support the use of this.
• 50:16Judgment and more widely in the
• 50:19in the upfront setting in hybrids
• 50:21in untreated stage, 4,
• 50:23three and four patients. Um,
• 50:25I just want to briefly briefly mention this.
• 50:28This trial,
• 50:29which was presented as a post office
• 50:31there is more that concept that was
• 50:34presented because this is an ongoing
• 50:37trial and we're part of it at Yale.
• 50:39He said as we just reviewed the
• 50:42addition of brentuximab window tint
• 50:45to avd improves PFS in advanced age,
• 50:48but still 15 to 20% patients are relapse,
• 50:51relapse or refractory and BV
• 50:54addition increases toxicity and
• 50:55require growth factors.
• 50:57So this is the this is the largest.
• 51:02North American Cooperative group
• 51:04trials in Advanced Hodgkin study that
• 51:08is being conducted in collaboration
• 51:11with Canada and even with the
• 51:14collaboration of the children.
• 51:16The theology.
• 51:19Patrick Oncology group for Hodgkin is
• 51:21a study that is planning to enroll
• 51:24987 patients and two randomized
• 51:27them either to nivolumab avd versus
• 51:29Brentuximab and Odin and Avd for six cycles.
• 51:33The patients are going to be satisfied
• 51:36based on the age Ipsy and intended
• 51:39use of radiation and the primary
• 51:41endpoint is progression free survival,
• 51:44but a lot of other data are planned
• 51:47to be gathered.
• 51:49And in particular,
• 51:50patient reported outcomes including fatigue,
• 51:52neuropathy, scoring and quality of life.
• 51:55So despite covid,
• 51:56it looks like the TARDIS.
• 51:58This trial is at the target of the
• 52:01expected accrual and the results
• 52:03of this trial are eagerly awaited.
• 52:05So let's move them to the salvage treatment.
• 52:08What's new in the salvage treatment?
• 52:11So usually provision that are relapsed
• 52:13refractory after the first line of
• 52:16treatment of the general approach is
• 52:18to proceed to salvage chemotherapy.
• 52:20Usually platinum based or genocide
• 52:22happen based with an expected
• 52:25response rate in the 5060% range with
• 52:27introduction of brentuximab concurrently
• 52:29or sequentially in the salvage regiment,
• 52:32we now expect responses in the
• 52:3460 and 70% range,
• 52:36but the use of a print aksamit now is
• 52:39getting limited by the fact that is
• 52:42used more widely in the first line
• 52:46and therefore alternative strategies
• 52:48that are being explored in this study.
• 52:51Specifically,
• 52:51is a face to study using bumper
• 52:54lizama in addition to our regular
• 52:57salvage treatment GD,
• 52:58which is one of the historically
• 53:01used salvage treatment as
• 53:02a second line for relapsed refractory
• 53:05article informal and eligibility
• 53:07dissipation that our love story factory.
• 53:10The first line of treatment.
• 53:12Primary endpoint is the PCR rate
• 53:15because that's the most important
• 53:17factor that we that we have to
• 53:20achieve after salvage treatment.
• 53:22With Adima to pursue to transplant.
• 53:25So patients received the regular GBD
• 53:28combination and they want and they ate
• 53:31with addition of populism on day one.
• 53:34After two cycles of patients
• 53:37but positive patient back,
• 53:38negative were allowed to
• 53:40pursue directly to transplant.
• 53:42Otherwise everybody received 4 cycle
• 53:45and then that was evaluated at the end
• 53:49of treatment before the transplant.
• 53:51So let's see what happened.
• 53:53There were 939 patients enrolled in this
• 53:55study, with a median age of 38 years.
• 53:58Importantly,
• 53:58most of the patients were advanced
• 54:00age of the initial diagnosis
• 54:02and the time of enrollment.
• 54:04When they relapsed,
• 54:05many patients had extranodal site,
• 54:061/3 of them extranodal sites
• 54:08of disease involvement,
• 54:09and the symptoms was present
• 54:11in 15% of the patient.
• 54:14Almost like 40% were refractory
• 54:16or either they relapsed in first
• 54:19year so very high risk patient
• 54:21population and the treatment they
• 54:23received up front was primarily ABVD,
• 54:26but some patients reserved receive the
• 54:28print axiom an and or Veeco approaches.
• 54:31So after the first 2 cycles
• 54:34of pembrolizumab T 92% of the
• 54:37patients were found to be in a CR,
• 54:40and that's unprecedented data
• 54:42for a salvage attachment.
• 54:44And after an additional 2 cycles and
• 54:47there was an additional CR rate,
• 54:49so the total see CR rate for this
• 54:52group of patients was 95 percent,
• 54:5595% proceeding to transplant and a
• 54:57good amount about a third of them
• 55:00preceded to maintenance with the
• 55:02print accent windowed in for a year.
• 55:05Based on the accurate trial study,
• 55:07an none of the patient with limited
• 55:10follow up that we have now for this
• 55:13study at progression of disease.
• 55:15After the transplant. So why this this?
• 55:18This regiment works so well.
• 55:20It even outperformed what checkpoint
• 55:22plus chemotherapy does in first line.
• 55:24Sony Vollmer Avd does not have the
• 55:27same efficacy and one of the reasons
• 55:30that the others are looking into
• 55:32is if there is anything specific in
• 55:35this may be the synergy between the
• 55:37chemotherapy agent that is unique to
• 55:39this regiment inside I mean with a
• 55:42checkpoint inhibitor in particular
• 55:43the ability of selectively eliminate.
• 55:46That my little derived suppressor cells,
• 55:48so these exciting results poised base
• 55:51for the next court on this study,
• 55:54were actually the aim is to treat
• 55:57everybody with Pembridge EBD for four cycles,
• 56:00and then skip the Trump's transplant
• 56:02altogether and have the patient instead.
• 56:05Being on maintenance with 13 cycles
• 56:07of pembrolizumab maintenance.
• 56:08So this is going to be very exciting to
• 56:13see what the outcome of this patient is.
• 56:17Moving forward,
• 56:18let's talk about consolidation after
• 56:20transplant. What's new in that?
• 56:21We know that patients at high risk
• 56:24of relapse after the transplant
• 56:25based on the characteristic primary
• 56:28refractory disease.
• 56:29As general involvement with symptoms
• 56:30of relapse order requiring more
• 56:32than one line of salvage treatment,
• 56:34not in CR, the time of transplant,
• 56:37they are higher risk of
• 56:39relapsing after transplant.
• 56:40So now there have been strategies
• 56:42that have been explored that
• 56:44to improve their PFS and.
• 56:46We all know about the if their trial
• 56:48where baby consolidation was was utilized
• 56:51after atleast himself transplant
• 56:53with an improvement of the PFS,
• 56:55although with a significant there
• 56:57was a 33% and drop off patients
• 57:00that could not complete the study
• 57:03due to neuropathy and another
• 57:05study that has been done used that
• 57:07embolism up in this setting.
• 57:09It was much smaller study only
• 57:11with 30 patient and patient
• 57:13population and better risk factors.
• 57:16So the apotheosis behind this study
• 57:18is to use the these two agents
• 57:21in combination Vivian Evil as
• 57:23consolidation and utilizing only
• 57:25eight cycles instead of the 16 cycles
• 57:28that was used in the fair trial,
• 57:31and again, patients that were enrolled,
• 57:3359 patients were enrolled in this
• 57:36trial and they were started on that.
• 57:39These are the combination between
• 57:41evil about them,
• 57:42between 30 and 6075 days after a transplant.
• 57:46And I just want to point out that there
• 57:49was a lot of patients that could not
• 57:53complete the eight cycles that were planned.
• 57:5759% could not complete the treatment
• 58:00plan and only 76% completed 8 cycles
• 58:03of either brentuximab or nivolumab.
• 58:06So the take home message from this,
• 58:09that is that the treatment the
• 58:12maintenance after transplant is a much.
• 58:15It is very difficult.
• 58:16Treatment too,
• 58:17for the patients to undergo as the side
• 58:21effects associated with the utilization
• 58:24of these agents in this setting.
• 58:27Is associated with an increased side effects,
• 58:30in particular immune related adverse
• 58:32event that we're seeing up to 27% of
• 58:36the patients enrolled in this study.
• 58:39But nevertheless,
• 58:39it's very encouraging that there is
• 58:42a 92% progression free survival in
• 58:45this high risk patients for relapse
• 58:48even despite their prior exposure
• 58:50either to BB and anti PD one.
• 58:53And since I want to leave sometimes
• 58:56for question.
• 58:57I'm just going to mention briefly
• 59:00that this study think the merit
• 59:02of this study has been literally
• 59:04to enroll older patients which
• 59:07are under representative in most
• 59:09of the Hodgkin lymphoma trial.
• 59:11They have less prognosis and unfortunately
• 59:14I mean it's not a randomized trial,
• 59:16so patients were received either BV
• 59:19in monotherapy or in combination with
• 59:21chemotherapy and just to be very,
• 59:24very quick.
• 59:25The take home messages that
• 59:27DV monotherapy has been with.
• 59:29Very, very active, but as shown,
• 59:31the employer in prior studies,
• 59:33the PFS,
• 59:34was not very long,
• 59:35whereas when we've is combined
• 59:37with chemotherapy,
• 59:38the risks are outside effects increases,
• 59:40but it is associated with
• 59:43that much longer PFS.
• 59:45The only thing that they want I
• 59:47like is that the brand tax amount
• 59:50window 10 plus bendamustine armor
• 59:52was closed due to an excess of
• 59:54toxicity is not a good treatment
• 59:56in this elderly population.
• 59:57And with this I left panel open for question.
• 01:00:06Thank you all for presenting.
• 01:00:08It was really quite comprehensive.
• 01:00:10We're going to go over our allotted
• 01:00:12hour and folks can stay in.
• 01:00:14Will have a little question answer period.
• 01:00:17While we're on the topic of Hodgkin,
• 01:00:19that was really nice.
• 01:00:21Presentation documents tomorrow.
• 01:00:22How do you interpret and
• 01:00:24how do you take together?
• 01:00:25You know the five year data
• 01:00:27on the TV
• 01:00:28and first line.
• 01:00:30Incredible salvage options
• 01:00:31for patients you know.
• 01:00:33How do you put that together when you
• 01:00:36have someone that has advanced stage
• 01:00:38first line has come before you are you?
• 01:00:41You know the five year data compelling
• 01:00:43you to give more BVD or you still doing
• 01:00:46adaptive kind of raffle approach?
• 01:00:50This is this is a very good question.
• 01:00:53Interesting isn't it? It's very I mean,
• 01:00:56one of the argument against intensifying
• 01:00:59Firstline treatment is that is so well
• 01:01:02tolerated and that we have so many,
• 01:01:04I mean salvage therapy works in our chicken.
• 01:01:08So in order to improve.
• 01:01:11A small percentage of the outcome
• 01:01:13of all the patients you end up
• 01:01:16like exposing a lot of patients
• 01:01:18to a more aggressive treatment.
• 01:01:20While you could have served salvage only
• 01:01:23to those that do not respond to a DVD.
• 01:01:27So, but I think that this this five
• 01:01:29year update I really like to see that
• 01:01:32the peripheral neuropathy was not
• 01:01:34was getting better progressively year
• 01:01:37after year and there were not major
• 01:01:40sequelae regarding that approach and.
• 01:01:42I really like the fact that there
• 01:01:44was no not not an increase of
• 01:01:47secondary malignancy or of. The.
• 01:01:52Any bad outcome on pregnancies,
• 01:01:54but what I really think is the value of
• 01:01:57this approach as compared to PET adopted
• 01:02:00one is that you don't need to adopt it.
• 01:02:04The PFS of patients that have a
• 01:02:06pet positive after 2 cycle is very
• 01:02:09good and is as good as the one that
• 01:02:12you get using escalated beacopp
• 01:02:14and especially population.
• 01:02:17That's
• 01:02:17a really nice summary and I have
• 01:02:20very similar feelings of that,
• 01:02:21so it's a complicated
• 01:02:23conversation that certainly
• 01:02:24patients should be presented both.
• 01:02:25Kind of adaptive Anet DVD
• 01:02:27and tailored to patient
• 01:02:29preferences and kind of a profile.
• 01:02:31Not surprisingly, there are a number of
• 01:02:33questions about CNS prophylaxis of Doctor
• 01:02:35Kothari can step
• 01:02:36up to the plate, but you know how?
• 01:02:39How do you interpret the
• 01:02:41two abstracts that were presented oral
• 01:02:43session? I know there was a lot of kind
• 01:02:46of discussion during that meeting.
• 01:02:48Has that informed how you
• 01:02:50approach patients that are
• 01:02:51high risk for sinas that
• 01:02:53relapse? I think both abstracts kind
• 01:02:55of confused us further. To be honest.
• 01:02:58I mean it's great set of data,
• 01:03:00especially the second set of data that I
• 01:03:03presented which is a multi institutional US.
• 01:03:06You know study where there are more
• 01:03:08than thousand patients so you know
• 01:03:10the the end was pretty good to have
• 01:03:13meaningful interpretation, but I think.
• 01:03:16Overall, I think my summary of,
• 01:03:19I think both both abstracts
• 01:03:21would be that we need better,
• 01:03:24stronger frontline regiments to
• 01:03:26eradicate the real high risk DCL from
• 01:03:30the get go because that eventually
• 01:03:33leads to a CNS relapse and that
• 01:03:36was shown through the Alberta,
• 01:03:38Canada study where patients who
• 01:03:41got intensive chemo immunotherapy.
• 01:03:43The trend was towards better
• 01:03:46CNS relapse rates.
• 01:03:48And I guess the same could be told
• 01:03:50even you know the fact that autologous
• 01:03:53stem cell transplant was helpful.
• 01:03:55So overall,
• 01:03:56I would say that this these abstracts
• 01:03:59don't change my practice of using
• 01:04:01high dose methotrexate with R
• 01:04:03CHOP or most likely into fecal
• 01:04:05methotrexate with those adjusted
• 01:04:07epoch in high risk blpi atients.
• 01:04:09What I would say I think,
• 01:04:11which was interesting to note,
• 01:04:13is the liver involvement
• 01:04:15and testicular involvement,
• 01:04:16which we traditionally don't.
• 01:04:18Think of it that way,
• 01:04:20although there are some
• 01:04:21scattered papers about it,
• 01:04:23I think this is just to highlight
• 01:04:25that you know liver and testicle
• 01:04:28involvement also portends
• 01:04:29higher CNS relapse rate.
• 01:04:32Thank
• 01:04:32you for that and then Doctor Safi.
• 01:04:35Really, I think lots of exciting
• 01:04:38early phase studies in T cell.
• 01:04:40But certainly I think we need kind of
• 01:04:43larger randomized prospective
• 01:04:44data and basically everyone with T cell
• 01:04:47lymphoma should be on
• 01:04:49protocol, right? If we're
• 01:04:51going to really
• 01:04:52start improving the
• 01:04:53outcomes, can you talk about
• 01:04:55some of the
• 01:04:56trials that we have open in T cell
• 01:04:59lymphoma either currently or in
• 01:05:02the future that? We hope to kind
• 01:05:04of increase our accruals for.
• 01:05:07Yes, absolutely. Actually we have.
• 01:05:09We do have a few exciting things
• 01:05:12coming down the Pike so we do use
• 01:05:15those adjusted epoch quite a bit for
• 01:05:18aggressive T cell lymphoma here at Yale.
• 01:05:22And so we have an IIT that is in the
• 01:05:25works which is which is funded and
• 01:05:28basically the protocol is being developed.
• 01:05:31And that's with those suggested
• 01:05:34epoch with mogamulizumab as frontline
• 01:05:36therapy in these patients and.
• 01:05:38So epoch does have overall, you know,
• 01:05:41looking at the chop response
• 01:05:43rates of like 3540% CR rates,
• 01:05:46epoch does tend to have a better
• 01:05:49overall response rate in CR rates in
• 01:05:52the 60% think you know 60% range.
• 01:05:55So the idea is really to try to get this.
• 01:06:00These patients and the deepest
• 01:06:02remission that you can and you know
• 01:06:06then then take them to transplants and.
• 01:06:09It's really an excited study.
• 01:06:11It is a phase two single arm study,
• 01:06:15but I think it's a novel combination
• 01:06:18that we're excited about.
• 01:06:20As far as the and one additional study
• 01:06:23would be in CD 30 positive patients
• 01:06:27looking at the combination of rituximab
• 01:06:30with pembrolizumab and that's kind
• 01:06:32of an idea that I wrote at Vanderbilt
• 01:06:36and Vanderbilt that we're hoping to open.
• 01:06:40In the coming months as well.
• 01:06:42As far as the present studies are concerned,
• 01:06:45the ones that we are still enrolling on,
• 01:06:49we have a couple of oral agents,
• 01:06:51including the DIETY study,
• 01:06:53which is basically an IDH one,
• 01:06:55IDH, two inhibitor.
• 01:06:57And it has to be.
• 01:06:59It has, you know,
• 01:07:00single agent activity in relapsed
• 01:07:02refractory T cell lymphoma,
• 01:07:04and definitely something that
• 01:07:05we've seen responses with,
• 01:07:07and sometimes it's just the right
• 01:07:09treatment to try to get these
• 01:07:11patients in remission,
• 01:07:12take take them to transplant.
• 01:07:16Thank you so much and this was great.
• 01:07:19Amazing talks and thanks God
• 01:07:21for this the moderation.
• 01:07:22The questions as you heard a
• 01:07:24lot of exciting developments
• 01:07:26going on in the informal work.
• 01:07:28We have a lot of actually
• 01:07:30active clinical trials,
• 01:07:31so feel free to reach out to any
• 01:07:33further Informa experts or any
• 01:07:35questions about your patience or
• 01:07:37any referrals for clinical trials.
• 01:07:39Reminder that a recording of this
• 01:07:41session will be available next
• 01:07:43week and along with the slides and
• 01:07:45should be an enduring material.
• 01:07:47For your future reference,
• 01:07:48next week will have the by Lloyd
• 01:07:50updates and thank you so much
• 01:07:52everyone and have a great weekend.
• 01:07:53Thank you.